Chimeric therapeutics, compositions, and methods for using same

Abstract

Chimeric therapeutics are disclosed that include a modified viral core protein comprising at least one mutation or modification in an immunogenic epitope and a therapeutic agent. The therapeutic agent may be associated with the modified viral core protein and may be a nucleic acid, a protein, or a small molecule. Also disclosed are particles and compositions that include the disclosed chimeric therapeutics.

What is claimed is: 
     
         1 - 94 . (canceled) 
     
     
         95 . A therapeutic particle comprising:
 a plurality of modified viral core proteins each comprising at least one mutation or modification in an immunogenic epitope, a structural core protein and a modified tail portion, wherein said structural core proteins form a capsid; and said modified tail portions are substantially dispose within said capsid; and   a plurality of nucleic acids, bound to said modified tail portion, wherein said nucleic acids are resistant to degradation with a nuclease when said particle is placed in aqueous solution.   
     
     
         96 . The therapeutic particle of  claim 95 , wherein said nucleic acids bound to said modified tail portion are substantially non-immunogenic. 
     
     
         97 . The therapeutic particle of  claim 95 , wherein said nucleic acids bound to said modified tail portion is bound with a binding affinity that allows release of said nucleic acids when said therapeutic particle is administered in vivo. 
     
     
         98 . The therapeutic particle of  claim 95 , wherein said particle comprises about 180 to about 250 viral core proteins. 
     
     
         99 . The therapeutic particle of  claim 95 , wherein said particle comprises about 170 to about 190 viral core proteins. 
     
     
         100 . The therapeutic particle of  claim 95 , wherein said particle comprises about 3 to about 50 nucleic acids. 
     
     
         101 . The therapeutic particle of  claim 95 , wherein said particle comprises about 6 to about 28 nucleic acids. 
     
     
         102 . The therapeutic particle of  claim 95 , wherein said particle is resistant to serum degradation in an aqueous serum solution. 
     
     
         103 . The therapeutic particle of  claim 95 , wherein a chemical linker moiety is bound to said capsid. 
     
     
         104 . The therapeutic particle of  claim 103 , wherein said chemical linker moiety is formed by contacting said capsid with PE-maleimide. 
     
     
         105 . The therapeutic particle of  claim 95 , further comprising a coating. 
     
     
         106 . The therapeutic particle of  claim 105  wherein said coating comprises one or more lipids. 
     
     
         107 . The therapeutic particle of  claim 105 , wherein the coating comprises cholesterol. 
     
     
         108 . The therapeutic particle of  claim 105 , wherein said coating comprises a neutral lipid. 
     
     
         109 . The therapeutic particle of  claim 105 , wherein said coating further comprises HSPC and/or POPG. 
     
     
         110 . The therapeutic particle of  claim 95 , wherein said viral core proteins are hepatitis B viral core proteins. 
     
     
         111 . The therapeutic particle of  claim 95 , wherein the modified viral core protein further comprises a modified C-terminal tail portion and/or a modified N-terminal tail portion. 
     
     
         112 . A pharmaceutically acceptable composition comprising a plurality of the therapeutic particles of  claim 95  and a pharmaceutically acceptable excipient. 
     
     
         113 . A method of regulating a specific target expression in a cell comprising administering to the cell a therapeutic particle or composition of  claim 95 . 
     
     
         114 . A method of treating or ameliorating a disease associated with a particular gene target in a patient in need thereof comprising administering to said patient a pharmaceutically effective amount of a composition comprising the therapeutic particles or compositions of  claim 95 .